JPH032550B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an adsorption type blood purifier in which an adsorbent layer is formed of a group of adsorbent particles coated with an acyl chitin film, and its main purpose is to
The aim is to improve the adsorbent layer and blood compatibility and adsorption performance. Conventionally, as a treatment for renal failure and liver failure, hemodialysis has been used to remove harmful and unnecessary substances from the blood. However, conventional hemodialysis methods have problems such as large dialysis machines, long dialysis times, large amounts of dialysate, and difficulty in removing medium-molecular-weight harmful and unnecessary substances. . As a method to solve the problems of conventional hemodialysis methods, there is a known method of adsorbing and removing harmful and unnecessary substances from the blood through direct perfusion of blood using adsorbents such as activated carbon and porous adsorbent resins. However, these adsorbents, by direct contact with blood,
There have been problems such as adsorption and coagulation of blood on the surface of the adsorbent, and fine powder of the adsorbent mixed into the blood and causing a reaction in the living body. In order to solve these problems, methods have been known in which the surface of the adsorbent is coated with a polymer film such as a nitrocellulose film, a cellulose acetate film, a gelatin film, or a polyhydroxyethyl methacrylate film. There is a risk that blood may be adsorbed and coagulated on the surface of the adsorbent due to contact, the adsorption performance of the adsorbent may be reduced, and the polymer membrane components may be eluted into the blood.
During high-pressure steam sterilization, the polymer film on the surface of the activated carbon may soften or deform. As a result of various studies to improve the above-mentioned problems, the inventors of the present invention have discovered that the blood in the adsorbent layer can be improved by using a group of adsorbent particles coated with an acyl chitin film as the adsorbent layer of an adsorption type blood purifier. They discovered that the compatibility and adsorption performance could be improved, and completed the adsorption type blood purifier of the present invention. Next, the configuration of the present invention will be explained in detail. As shown in the drawings, the present invention is an adsorption type blood purifier 1 characterized in that an adsorbent layer 2 is formed of an adsorbent particle group coated with an acyl chitin film. The drawing is a partially sectional front view of an embodiment of the adsorption type blood purifier of the present invention. In the drawing, 1 is an adsorption type blood purifier, 2 is an adsorbent layer, 3 is a superlattice, and 4 is a superlattice.
is a rectification chamber, 5 is a perfusate inlet, and 6 is a perfusate outlet. The blood purification method using the adsorption type blood purifier of the present invention will be explained with reference to the drawings. In other words, perfusate (blood or plasma) is introduced into the blood purifier 1 from the perfusate inlet 5, and the rectifying chamber 4 It then passes through the superlattice 3 and is distributed on the adsorbent layer 2, where harmful and unnecessary substances in the perfusate are adsorbed and removed.
Next, the purified perfusate passes through the overgrid on the opposite side, fills the rectification chamber, is led out from the perfusate outlet 6, and, if the perfusate is blood, is returned to the living body through the veins. If the perfusate is a liquid, it is combined with blood purified by filtration and returned to the body through the veins. In the present invention, the adsorbent particles forming the adsorbent layer are activated carbon particles, porous adsorption resin particles (for example, styrene-divinylbenzene copolymer resin, polyacrylic acid ester resin, etc.) particles, ion exchange resin particles, etc. Spherical bodies with a particle size of 0.1 to 2 mm are preferred. Examples of the acyl chitin used in the present invention include formalyl chitin, acetyl chitin, propitinyl chitin, butyryl chitin, caproyl chitin, caprylic chitin, lauroyl chitin, benzoyl chitin, etc., and it is possible to form a film from a solution thereof; The formed acyl chitin film can prevent adsorbent fragments or fine particles from entering the blood, and the acyl chitin itself is essentially non-reactive to living organisms and anticoagulant to blood. It has characteristics such as not causing blood coagulation even if it comes into direct contact with blood on the surface of the acyl chitin film. In addition, the acyl chitin film used in the present invention has water resistance and heat resistance, so it does not elute into blood or aggregate with adsorbents, and does not soften or soften during high-pressure steam sterilization.
No deformation occurs. In the present invention, the method of coating the adsorbent with an acyl chitin film includes spray coating the adsorbent particles with an acyl chitin solution while rolling the adsorbent particles using a coating pan, and mixing by rolling. A method of partially removing the solvent with hot air, then dispersing it in a non-solvent to leach the remaining solvent, and coating the adsorbent particles with an acyl chitin film. A method in which the adsorbent particles are immersed and mixed in an acyl chitin solution. Next, there is a method in which the adsorbent particles are coated with an acyl chitin film by evaporating a part of the solvent with hot air after evaporation or centrifugation, and then dispersing the adsorbent in a non-solvent to leached the solvent. The acyl chitin film formed by these coating methods has a network structure, does not reduce the adsorption performance of adsorbent particles, and has the effect of preventing adsorption and coagulation of blood on the adsorbent surface. The method for forming the adsorbent layer in the present invention is as follows:
As shown in the drawing, there is a method in which adsorbent particles coated with an acyl chitin film are filled between two superlattices in the container body, thereby reducing the pressure loss of the perfusion fluid in the adsorbent layer. Moreover, it can be distributed in a uniform distribution state. The amount of adsorbent particles used in the present invention varies depending on the purpose of use, form of use, method of use, etc., but is suitably 50 to 500 g. The adsorption type blood purifier of the present invention can be applied to direct blood perfusion methods, blood perfusion methods, and the like. In other words, in the direct blood perfusion method, blood flowing out from the artery side of a living body is introduced into a blood purifier via a blood circuit, and then directly perfused into an adsorbent layer in the blood purifier to eliminate harmful substances in the blood.・This is a method in which unnecessary substances are adsorbed and removed, and then the purified blood is perfused into the veins of the body. Also, if you explain the blood flow method,
Blood flowing out from the arterial side of the living body is introduced into the blood filter via the blood circuit, plasma components containing harmful and unnecessary substances in the blood are passed through the membrane in the blood filter, and the liquid is passed through the recovery channel. The purified liquid is introduced into the blood purifier via the blood purifier, perfused into the adsorbent layer in the blood purifier to adsorb and remove harmful and unnecessary substances in the liquid, and then the purified liquid is merged with the blood circuit via the purified liquid outlet. The blood flows back into the veins of the body together with the filtered blood. On the other hand, excess fluid is excreted out of the body via fluid excretory channels. Next, the effects of the adsorption type blood purifier of the present invention will be listed. (a) The adsorption type blood purifier of the present invention can be applied as an artificial kidney or artificial liver using a direct blood perfusion method, a blood fluid method, or the like. (b) The acyl chitin membrane used in the present invention does not soften, deform, or decompose during high-pressure steam sterilization, and does not contaminate perfusate (blood or fluid). (c) The adsorbent layer used in the present invention can circulate blood without adsorbing or coagulating blood, and can efficiently adsorb and remove harmful and unnecessary substances in blood. Next, the present invention will be explained by examples. Example 1 150 g of spherical porous adsorption resin (styrene-divinylbenzene copolymer resin) particles with a particle size of 0.3 to 0.6 mm were
Acetyl chitin was immersed and mixed in a 1% formic acid solution with a degree of acetylation of 2.0, and then the excess acetyl chitin solution was removed by filtration, a portion of the formic acid was evaporated with hot air, and the adsorbed resin particles were removed. The formic acid was eluted by dispersing it in ionized water, filtered, and thoroughly washed with water to coat the adsorbed resin particles with an acetyl chitin film. Adsorbent resin particles coated with an acetyl chitin film were filled into a polypropylene resin container as shown in the figure to form an adsorbent layer between two superlattices. Next, the container was filled with physiological saline, air bubbles in the container were removed, and the entrance and exit port were tightly plugged. Next, high-pressure steam sterilization treatment (121°C, 30 minutes) was performed to obtain an adsorption type blood purifier. Using the obtained blood purifier, an artificial organ device was assembled by connecting a blood circuit, a blood pump, a pressure gauge, etc. Next, using 200 mg/dl pentobarbital phosphate buffer solution (PH7.4) 10, the adsorption capacity was determined by direct perfusion method (200 ml/min perfusion method at 37°C).
Performed in vitro experiments. For comparison, a blood purifier with a similar configuration was prepared using adsorbent resin particles coated with a cellulose acetate membrane and raw adsorbent resin particles, and an in-vitro experiment of adsorption capacity was similarly conducted. As shown in Table 1, the adsorption capacity comparison experiment results show that the adsorption capacity of a blood purifier using adsorption resin particles coated with acetyl chitin membrane is on the same level as that of a blood purification device using raw material adsorption resin particles. The adsorption capacity was superior to that of a blood purifier using adsorption resin particles coated with cellulose acetate membrane. Table-1
is a comparison table of pentobarbital adsorption capacity (adsorption amount in percentage).

[Table] In addition, an artificial organ device was assembled in the same manner as above using three types of blood purifiers, and then a direct blood perfusion method (perfusion for 2 hours at 37°C) was performed using a mongrel liver-impaired dog.
In-vivo experiments were carried out. As shown in Table 2, the experimental results show that blood composition changes in the blood purifier using acetylchitin-coated adsorbent resin particles are different from blood purification using cellulose acetate membrane-coated adsorbent resin particles and raw material adsorbent resin particles. The blood compatibility of the adsorbent resin particles coated with acetyl chitin was superior to that of the blood component change in the blood vessel. Table-2
This is a comparison table showing the reduction rate (%) of white blood cell count and platelet count due to direct blood perfusion for 2 hours.

[Table] Example 2 150 g of spherical activated carbon particles having a particle size of 0.6 to 0.8 mm were coated with an acetyl chitin film in the same manner as in Example 1 using a 1% formic acid solution of acetyl chitin with a degree of acetylation of 2.0. Activated carbon particles coated with an acetyl chitin film were filled into a polycarbonate resin container to form an adsorbent layer between two superlattices, as shown in the figure. Next, the container was filled with physiological saline, air bubbles in the container were removed, and the entrance and exit port were tightly plugged. next,
An adsorption type blood purifier was obtained by high-pressure steam sterilization (121°C, 30 minutes). Using the obtained blood purifier, an artificial organ device was assembled by connecting a blood circuit, a blood pump, a pressure gauge, etc., and a blood purification experiment was conducted using the direct blood perfusion method. As a result, harmful and unnecessary substances in the blood can be efficiently and selectively adsorbed and removed, and adsorption and coagulation of blood components on the surface of activated carbon particles can be prevented.In short, efficient blood purification is possible. It was hot.

[Brief explanation of the drawing]

The drawing is a partially sectional front view of an embodiment of the adsorption type blood purifier of the present invention. In the drawing, 1 is an adsorption type blood purifier, 2 is an adsorbent layer, 3 is a superlattice, 4 is a rectifier, 5 is a perfusate inlet, and 6 is a perfusate outlet.

Claims (1)

[Scope of Claims] 1. An adsorption type blood purifier, characterized in that the adsorbent layer is formed of a group of adsorbent particles coated with an acyl chitin film. 2. The adsorption type blood purifier according to claim 1, wherein the acylchitin film is composed of fluoroylchitin, acetylchitin, propionylchitin, butyrylchitin, caproylchitin, caprylicchitin, lauroylchitin, or benzoylchitin. 3. The adsorption type blood purifier according to claims 1 and 2, wherein the acyl chitin membrane has a network structure.